Shikonin regulates autophagy via the AMPK/mTOR pathway and reduces apoptosis of human umbilical cord mesenchymal stem cells to improve survival in tissues surrounding brain contusion

Autor: Ke Wu, Linhui Ruan, Junnan Ru, Kankai Wang, Zhezhe Sun, Qichuan Zhuge, Lijie Huang, Xiaohong Zhu
Rok vydání: 2021
Předmět:
Zdroj: Experimental and Therapeutic Medicine
ISSN: 1792-1015
1792-0981
DOI: 10.3892/etm.2021.10910
Popis: Shikonin has been reported to regulate autophagy via the AMP-activated protein kinase (AMPK)/mTOR signalling pathway and decrease apoptosis in transplanted human umbilical cord mesenchymal stem cells (HUMSCs). In the present study, HUMSCs were exposed to oxygen glucose deprivation (OGD) in vitro for 12 h, and TUNEL fluorescence staining was used to detect apoptosis. Differences in autophagy and AMPK/mTOR pathway-related protein expression following treatment with shikonin were quantitatively analyzed by western blotting. Green fluorescent protein-labelled stem cells were implanted into traumatic brain injury-model mice and the survival of HUMSCs was observed after 7 days. Shikonin increased the number of cells in brain tissue surrounding the contusion 7 days after transplantation. Furthermore, shikonin treatment decreased apoptosis, increased the expression of autophagy-related proteins, increased phosphorylated AMPK expression and downregulated phosphorylated mTOR expression. In addition, the autophagy inhibitor 3-methyladenine attenuated these effects and aggravated apoptosis. Subsequently, shikonin upregulated autophagy and protected HUMSCs in the area surrounding contused brain tissue. Shikonin may regulate autophagy via the AMPK/mTOR signalling pathway and protect transplanted HUMSCs from apoptosis induced by hypoxia/ischemia.
Databáze: OpenAIRE
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